Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04966468 |
| Other study ID # |
542-2019-OSS-AUSLBO |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
December 14, 2020 |
| Est. completion date |
March 31, 2022 |
Study information
| Verified date |
August 2021 |
| Source |
Fondazione ANT Italia ONLUS |
| Contact |
Rita Ostan, PhD |
| Phone |
+39 3487900191 |
| Email |
rita.ostan[@]ant.it |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Oncological disease, in addition to undermining the physical health and autonomy of the
patient, is often accompanied by significant anxious and depressive symptoms that can
compromise the quality of life of both patient and his/her family, hindering the adherence to
treatment, the effectiveness of therapies and worsening the clinical prognosis.
Several studies confirm that a large number of cancer patients experience severe levels of
psychological distress, with an average prevalence of any mood disorder ranging from 29% in
palliative care to 38% in oncological and hematological settings.
The advanced stages of the disease are characterized by a progressive loss of functional
autonomy, forcing the patient to a condition of isolation and both sensory and relational
deprivation. The reduction of the occasions in which it is possible to experience positive
emotions and meaningful social interactions often corresponds to an intensification of
obsessive worries and thoughts, which in turn increase stress and connect to further negative
emotional experiences. Thus the patient can be trapped in a vicious circle, that might
increase the worsening of quality of life.
In the last years, alongside traditional interventions, the effectiveness of interventions
based on the use of immersive audiovisual technologies has been tested, such as the use of
virtual reality (VR), which have the ability to emotionally involve the person, capture
his/her attention and direct it towards positive stimuli, without particular effort to be
used.
Compared to 2D or 3D videos, VR gives to the user a "greater degree of presence", giving the
impression of being immersed in a reality different from the real one. Unlike any other form
of psychological intervention, VR does not require special training to be used and has the
advantage of being used even in situations of poor mobility or attention capacity.
Available literature shows how the use of VR for cancer patients is a widespread practice
that can be considered an additional psychological technique. Several studies showed that VR
can help in decreasing the psychophysical symptoms usually experienced by cancer patients in
different settings (e.g., chemotherapy sessions, invasive medical procedures, and
hospitalization). However, up to now, there are no studies in the scientific literature on
the use of VR in the context of home palliative care. In this setting, it could be extremely
interesting to test the effectiveness of this innovative technology, due to its growing
diffusion and accessibility.
The present study is aimed at assessing the effects of VR in cancer patients followed by ANT
Foundation home palliative care program. The VR headset will be kept at the patients' home so
that he/she can use it in moments of greatest psychophysical discomfort (e.g., pain peaks,
moments of anxiety or sadness). The VR will contain both non-interactive and interactive
contents, the last ones specifically developed for ANT patients.
Description:
Background Many cancer patients experience severe levels of psychological distress, with a
percentage varying from 10-15% to 20-40% (Mitchell et al., 2011; Shim et al., 2018). The
average prevalence of mood disorders ranges from 29% in palliative care settings to 38% in
cancer and hematological contexts (Jacobsen et al., 2005). In addition to the emotional
distress, the advanced stages of the disease often imply a progressive loss of functional
autonomy (Dong et al., 2016). This put the patient in a status of deprivation and forced
isolation from relational and social aspects that were hitherto in their lives. This
psychological distress naturally adds to the burden of the physical symptoms caused by the
disease and/or invasive therapies, above all pain.
In the last years, technological innovation has allowed new solutions to meet old and
emerging needs in the healthcare field. One of these is represented by Virtual Reality (VR),
a non-invasive simulation technology that allows the user to be immersed in a multisensory
experience. VR technologies can emotionally involve the patients, inducing a positive mood
and allowing them to feel like a part of the virtual environment (Malloy and Milling, 2010;
Pourmand et al., 2018; Ahmadpour et al., 2019). The distraction effect is recognized to be
the primary principle underlying the effectiveness of VR (Schneider et al., 2004; Malloy and
Milling, 2010; Wiederhold et al., 2014; Bani Mohammad and Ahmad, 2019), as it is capable of
diverting patient's attention from his or her current clinical condition. Natural contents
have been shown to induce relaxation and restore work productivity, based on the Attention
Restoration Theory (Kaplan, 1995; Berto, 2005; Anderson et al., 2017). Moreover, water scenes
with views and sound seem to be more appreciated than scenes without water (White et al.,
2010; Anderson et al., 2017). Additionally, interactive contents could be even more effective
in their distraction-based effect than contents that only require passive observation
(Wiederhold and Wiederhold, 2007; Shahrbanian et al., 2012; Wender et al., 2019). VR-based
interventions are a convenient solution, as they do not require complicated training to be
used and can be employed in case of low mobility conditions.
VR has been used as an adjuvant treatment in various clinical conditions to relieve pain,
anxiety, and depression (Dascal et al., 2017; Fodor et al., 2018), during invasive procedures
(Hoffman et al., 2011; Shetty et al., 2019; Brown and Foronda, 2020), for chronic pain
management (Wiederhold et al., 2014; Pekyavas and Ergun, 2017) and in rehabilitation settings
(Shahrbanian et al., 2012; Lee et al., 2015). It has been extensively employed in promoting
cancer patients' psychological well-being (Chirico et al., 2016; Zeng et al., 2019; Ioannou
et al., 2020). Previous studies assessed the effects of VR in relieving cancer-related
symptomatology mainly in clinical settings (Li et al., 2011; Baños et al., 2013; Mosadeghi et
al., 2016; Bani Mohammad and Ahmad, 2019), alleviating anxiety and improving mood states.
Studies in palliative care (PC) have proven the acceptability of VR interventions (Oyama,
1997; Brungardt et al., 2020; Weingarten et al., 2020) and their effect in reducing
short-term symptoms (i.e., pain, drowsiness, lack of appetite, shortness of breath,
depression, anxiety, and well-being) (Niki et al., 2019; Johnson et al., 2020).
The evidence about the use of VR in a home PC program is still insufficient. To fill this
gap, the National Tumor Assistance Foundation (ANT), a non-profit organization working in
Italy in the field of home PC and pain management, conducted a pilot study to test the
feasibility of VR interventions for cancer patients assisted at home (Varani et al., 2018).
This was the first attempt to introduce VR interventions in home-PC settings, obtaining
promising results: most participants (73%) declared that they would be willing to keep a VR
headset at home; patients showed a 20% decrease in anxiety and depression and a significant
reduction of perceived pain and fatigue symptoms. As a further outcome, ANT collected
patients' preferences as the output of a focus group and semi-structured interviews: all
patients declared to prefer natural and relaxing scenarios, 36% expressed a preference for
interactive videos, while 33% wanted to see videos as simple observers (Sichi et al., 2019).
After these encouraging results, ANT introduced the VR headset with interactive and
non-interactive contents in its home-care practice.
VR use is not intended as a substitute for psychological support, but as an additional and
complementary intervention to allow the patient to have moments of leisure and distraction
from their psycho-physical condition.
Study design The proposed investigation is a randomized, controlled, non-profit,
single-center exploratory intervention study without drugs.
The study is aimed to evaluate the effect of immersive VR use on the psycho-physical symptoms
of cancer patients assisted by the ANT Foundation home palliative care program.
Patients who meet the inclusion criteria will be randomly assigned to one of the following
two groups:
Experimental group (VR group): patients will be given the VR headset with non-interactive and
interactive contents at home for four days
Control group (CTR group): patients will be given a tablet at home for four days with
relaxing non-interactive 2D videos with natural and artistic scenarios.
VR and CTR patients will undergo the same tests in the same time frame.
Primary outcome
- Anxiety and depression levels.
Secondary outcome
- Pain.
- Short-term psychophysical symptoms.
- To identify the type of immersive VR content and the average VR time-usage resulting
most beneficial for the home palliative care cancer patient.
Study population and setting The study population consists of cancer patients assisted by the
home palliative care program of the ANT Foundation in Bologna city and surrounding areas
(Italy). The study will take place directly at the patients' homes.
Randomization The investigators (ANT psychologists), after having exposed the study, will ask
the ANT physicians to identify patients who meet eligibility criteria among their assisted
ones. The physicians will explain the study to eligible patients and, if they show interest
to participate, they will be contacted by the psychologist. Patients will be randomly
assigned by the Research Department of the ANT Foundation to the VR group (30 patients) or
the CTR group (30 patients) by randomization using a series of random numbers generated by
Excel. Investigators that will run the statistical analysis will be blinded to the
randomization procedure.
Procedure and measures The study will last for four days for each patient. On the first day
(T0) each subject will be fully explained the study, given the specific information, and
asked to sign the informed consent. The psychologist, after filling the socio-demographic and
clinical data sheet, will ask the participant to answer the following set of validated
questionnaires which will then be administered for the second time at the end of the 4 days
of observation (T1). The procedure takes approximately 30 minutes at T0, and 10 minutes at
T1.
Hospital Anxiety and Depression Scale (HADS)
Brief Pain Inventory (BPI)
VR Group. After having filled the questionnaires, the investigator will show the patient how
to use the VR headset, suggesting using it especially in moments of psycho-physical
discomfort. In this study, a Lenovo Mirage Solo Headset, together with the wireless Daydream
motion controller, will be used. The VR headset will be kept at home by the patient for the
duration of the study (i.e., four days). The VR headset will be equipped with 10
non-interactive videos and a short interactive game. The videos are characterized by relaxing
scenarios (e.g., beach, sunset over the sea), giving a "passive" use to the patient. The game
is also characterized by a relaxing scenario and it will require the active interaction of
the patient. At the end of the observational period, the investigator will be able to
download the usage data to detect useful information, i.e., knowing if the patient has used
the VR headset to view interactive or non-interactive contents and the time of use. Before
and after each use of the VR headset, the patient will be asked to fulfill the Edmontom
Symptom Assessment Scale (ESAS), an internationally validated rating scale used to assess the
impact of the main symptoms on the quality of life in patients in palliative care. The ESAS
is composed of some numerical rating scales (NRS) relating to specific symptoms ranging from
0 (absence of the symptom) to 10 (worst symptom severity). The evaluated symptoms are pain,
nausea, depression, anxiety, drowsiness, lack of appetite, malaise, and shortness of breath.
In order to ensure the correct completion of the ESAS scales, it will be digitally inserted
directly into the VR headset, and the patient can answer by selecting the answer navigating
with the controller. Without filling the scale, the patient will not be able to access the
contents. On T0, the patient will be also asked to wear, for the entire duration of the
study, a wearable device, the Empatica E4 wristband, that measures several physiological
parameters (skin conductance, heart rate, skin temperature) associated with painful
experiences and anxious symptoms. Patients will be also provided with a short paper diary in
which they can record any pain or anxiety peak experienced during the day, as well as any
drug taken to overcome such moments of psychophysical discomfort (e.g., painkillers,
benzodiazepines). On the second day, the investigator goes back to the patient in order to
download data from Empatica E4 wristband and recharge it. On day T1, the patient will return
the VR headset and the wristband to the investigator and will complete again the HADS and BPI
questionnaires.
CTR group. After having administered the questionnaires, the investigator will illustrate to
the patient how to use the tablet for watching videos, suggesting using it especially in
moments of psycho-physical discomfort. The tablet will be given to the patient for the
duration of the study (four days). The tablet will be equipped with 10 non-interactive 2D
videos characterized by relaxing settings with natural or artistic scenarios, giving a
"passive" use to the patient. Before and after each use of the tablet, the patient has to
complete the ESAS digitally inserted into the tablet. The patient can answer by selecting the
answer on the touchscreen. Without filling the scale, the patient will not be able to access
the videos inserted in the tablet. On day 4 (T1), the patient will return the tablet to the
investigator and fill out the HADS and BPI questionnaires.
Security precautions The risk analysis, and the subsequent control measures, are based on the
device documentation provided by the manufacturer, the scientific literature, and the
evidence and experience gained with the Look of Life pilot study, conducted by ANT and the
University of Padova. In order to cover potential risks for patients, ANT Foundation has
taken out a study-specific insurance policy.
- Risk from electromagnetic emissions from VR headset. The investigators consider this
risk to be an acceptable level, given the European Certification (EC) of the device. The
device complies with the European Directive 2014/53/EU. Its Specific Absorbance Rate
(SAR) is 0.097 W/Kg (maximum for European standards for mobile devices 2 W/Kg).
- Mechanical risk. When wearing the device, the user is not able to see the real
surrounding space and could therefore trip or bump into objects. The instructions
suggest using the headset in an environment free from obstructions such as objects and
furniture. The device also gradually begins to obscure the view when the user moves more
than 0.4 m from the position selected as the central position and darkens completely
beyond 0.8 m. As an additional safety measure, investigators will instruct participants
to use the headset only when seated, thereby reducing the risk to an acceptable level.
- Nausea and motion sickness. In some cases, especially with particular contents and in
predisposed subjects, VR can elicit some episodes of nausea reported in the scientific
literature. However, in the pilot study conducted by ANT and the University of Padova,
no patient reported side effects due to the use of the VR headset. The investigator will
immediately stop the study if the patient shows any episodes of nausea or motion
sickness. The videos have been selected as they contain minimal stimuli that can elicit
motion sickness or emotional distress. All videos and interactive content within the VR
headset were created by Immerxive, a company specialized in the creation of multimedia
content, under the supervision of the ANT psychologists who had participated in the
pilot study. Furthermore, suffering from nausea or motion sickness are also exclusion
criteria for participation in the study.
- Risk of infection. The VR headset is worn in contact with the user's face, therefore it
could be a vehicle for infective agents among the study participants. Cleaning procedure
will adhere to the guidelines of the regional health and social agency of Emilia Romagna
(Agenzia sanitaria e sociale regionale dell'Emilia Romagna) concerning the disinfection
of medical devices and equipment. The investigators considered the headset, as it is in
contact with the user's face, as an oxygen therapy mask, for which the disinfection with
chlorine derivatives at a concentration of 0.1% is recommended. Before each use from
each subject, the VR headset will be disinfected with disposable sanitary wipes and the
lenses will be cleaned with specific alcohol-based products. The controller, the tablet
for the control group, and the wristband will be also disinfected after each patient
use.
- Seizures. Diagnosis of epilepsy, other neurological diseases, and sensitivity to
flashing lights are exclusion criteria for participation in the study.
- Eye fatigue, skin problems. ANT investigators, as already present in the device user
manual, advise participants against prolonged use and indicate to wear the headset on
clean and dry skin, and stop using it in case of signs of irritation, swelling, eczema,
or itching.
- Fraudulent access to data. The headset and the tablet record information on the time of
use of the device and on the assessments on the clinical scales carried out before and
after each session. As a control measure, the data are stored on the device anonymously.
Once the experimental phase for each subject is completed, the investigator sends a .txt
file to the email address specifically set up for receiving these reports from the
device restricted area (accessible only for the investigators by providing a password).
Once archived, the file within the device is deleted before the next use by a new
participant in the study.
For both groups, patients are aware through informed consent about the possible adverse
events (i.e., nausea, dizziness, motion sickness). The investigator keeps in contact with
patients for the whole study duration to immediately record any adverse event.
To cover the risks of adverse events described below, ANT Foundation has subscribed a
study-specific insurance policy.
Sample size The sample size was evaluated using G*power software with a-priori power analysis
for a one-sample Mann-Whitney-Wilcoxon test. Considering an α = 0.05 and a power 1-β = 0.80
with an effect size of 0.80, two groups of 27 patients each need to be enrolled for the
study. Considering a 10% dropout rate, the study aims to recruit a total of 60 patients (30
patients for the VR group + 30 patients for the CTR group).
Statistical analysis Statistical analysis will be conducted on the data after their
anonymization. An investigator is in charge of anonymization and blinding to groups patients
allocation. The anonymized and blinded data will be passed to the investigators in charge of
data analysis. Anonymized data will be stored within the Research Department of ANT
Foundation in an ad-hoc safe electronic database.
A descriptive analysis of the socio-demographic and clinical data of the patients at T0 will
be considered: age, marital status, educational qualification, occupation, neoplasm primary
site, the extent of the neoplasm, Karnofsky index, and drugs intake. Comparison analysis on
changes in anxiety, depression, and pain will be performed using mixed-effects models or
non-parametric statistical tests (e.g., Mann-Whitney-Wilcoxon). Similarly, changes in
short-term psychophysical symptomatology before and after the use of the VR headset/tablet
will be evaluated using mixed-effects models. The sociodemographic and clinical
characteristics of the subject, the type of VR content, and the usage times will be carried
out by adding covariates to the mixed-effects models. The analysis will follow the "intention
to treat" analysis.
Timeline
The project is scheduled in 3 phases:
- Phase 1 (1 month) - Training and patients selection - After the registration of the
study protocol, the investigators (ANT psychologists) will explain to the ANT physicians
the rationale, the protocol, the eligibility criteria of the study and will verify with
each of them the presence of patients that can be enrolled.
- Phase 2 (8 months) - Recruitment and data collection - Each physician will contact
eligible patients and ask them to participate. If the patient agrees, the physician will
provide the patient contact data to the psychologist who will contact him/her. The
psychologist will bring the VR headset or the tablet to the patient's home and will
enroll the patient in the study.
- Phase 3 (4 months) - Statistical analysis and publication - The data collected will be
statistically processed by the Research Department of the ANT Foundation for publication
in scientific journals of the sector. The publication of the trial results will follow
the CONSORT checklist.
Data management
- Data from electronic clinical scale assessment. Patients from both groups are asked to
fulfill the Edmonton Symptoms Assessment Scale before and after each use of the device.
These data are stored locally in the device and then sent to a pre-specified email
address specifically generated for this purpose. ANT investigator can access the data
within the device by entering the restricted area with a password.
- Data from Empatica E4 wristband. Physiological signals recorded by the smart wristband
are recorded and stored locally. On day 2 and day 4, the investigator download data to
the Empatica proprietary cloud platform and then locally
- Electronic records. Fulfilled questionnaires at T0 (day 1) and T1 (day 4) (HADS and BPI)
and information about information by the Case Report Form (CRF) are reported digitally
in a folder shared with all the investigators. Data are completely anonymized.
